• Xinyu Zhang, Zhibin Fu, and Chaoguang Yan.
• Shandong University of Traditional Chinese Medicine, China.
• Medicine (Baltimore). 2022 Dec 9; 101 (49): e31998e31998.

RationaleCytokine release syndrome (CRS) is an immune hyperactivation phenomenon in immunotherapy and, unlike other immune-related adverse events, only a few case reports have documented CRS due to the use of immune checkpoint inhibitors. In this article, we report a case of 2 episodes of CRS and delirium caused by pembrolizumab in a short period of time. This helps clinicians to understand CRS and to improve the diagnosis and treatment of immune-related adverse events.Patient ConcernsA 67-year-old patient with lung cancer developed fever, delirium, acute renal insufficiency, and acute cardiac insufficiency after 9 cycles of pablizumab therapy, and reappeared with these symptoms 1 week after improvement with glucocorticoid therapy.DiagnosesThe patient presented with concomitant cardiac insufficiency, hepatic and renal failure, delirium with high C-reactive protein levels and the patient's response to glucocorticoids, and exclusion of cerebrovascular accident and severe infection, resulting in a final diagnosis of CRS.InterventionsGlucocorticoid therapy and symptomatic support treatment.OutcomesAfter 2 hospitalizations, the patient did not develop CRS.LessonsTo our knowledge, this is the first case of delirium and CRS that occurred twice in a short period of time. This patient had no immune-related adverse reactions during the previous 9 immunotherapy sessions. This adverse reaction occurred after the inflammation of the wisdom teeth and was presumed to be related to an overstimulation of the immune response due to infection. Premature discontinuation of hormones for the patient's 1st treatment of CRS may be the reason for the 2nd occurrence of CRS. Therefore, timely and full course of glucocorticosteroids is a key therapeutic measure to cause CRS after the use of immune checkpoint inhibitors.Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.

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